Adenovirus vectors have shown promise for vaccines, but one key hurdle is preexisting immunity to these viruses in humans. The VRC has been investigating the use of DNA priming and the use of alternate adenoviral serotypes or modified adenoviral vectors to overcome prior immunity. During the past year, the VRC has evaluated various modifications to Adenovirus serotype 5 and 35 vectors to determine if they remain immunogenic while reducing the impact of prior exposure to Ad5.